Metformin effective for adolescents with PCOS: two small studies

Nicholas Mulcahy
PHILADELPHIA — Metformin is a helpful treatment for adolescents who either have polycystic ovarian syndrome or are at risk for the condition, according to two new studies with small patient sample sizes presented at the annual meeting of the Endocrine Society.

“In our placebo-controlled study, the girls [with PCOS] treated with metformin had a significant lowering of testosterone and a [slight] but not significant reduction in insulin levels,” said Dr. Celia Rodd. The control group with PCOS had no lowering in the testosterone levels, added Dr. Rodd, associate director, pediatric endocrinology, McGill University, Montreal.

Also, nearly all girls on metformin had at least one period during the 3-month study, compared with only about one-third of the control group.

“This is a good indication that the metformin was helpful and was so in most of the girls. Many of these girls hadn’t had a period for 6-18 months prestudy,” she said.

In the other study, European researchers used metformin in adolescent females who were at high risk for PCOS due to low birth weight and to having developed pubic hair at age 6 or 7 years, indicating precocious pubarche.

“We are reporting the first evidence that early metformin therapy prevents progression from precocious pubarche to PCOS in girls who were formerly small for gestational age or low-birth-weight babies,” according to Dr. Lourdes Ibanez of the University of Barcelona (Spain).

In Dr. Rodd’s study of adolescents with hyperinsulinemic, nondiabetic PCOS, 22 patients (aged 14-18 years) were randomly assigned to take either metformin 750 mg twice daily or placebo in a double-blind fashion for 12 weeks.

At the start of the study, the young women were moderately obese (mean body mass index was 32), had elevated serum levels of testosterone (mean 6.3 nmol/L), and were hirsute and oligomenorrheic. The average level of insulin during the oral glucose tolerance test was elevated (911 pmol/L). With metformin treatment, the insulin area under the curve significantly decreased by 30% and the testosterone level significantly decreased by 30%. The girls given placebo had no significant change in insulin or testosterone levels, said Dr. Rodd.

With regard to menstruation, 10 of 11 young women (91%) on metformin had at least one period during the 3-month study, compared with only 3 of the 11 girls (27%) in the control group, she said about the oligomenorrheic study participants.

No changes were noted in either group in body mass index, hirsutism score, blood pressure, or lipid profiles. The metformin group had few side effects, Dr. Rodd said.

In Dr. Ibanez’s study of adolescents at risk for PCOS, 24 girls were randomized to either metformin (850 mg) or no treatment for 12 months. The girls had a low mean birth weight (2.4 kg), presented with precocious pubarche (mean age of 6.7 years), were currently postmenarcheal (mean age of 12.4 years), and had hyper-insulinemic hyperandrogenemia but were nonobese.

In the 12 untreated girls at risk for PCOS, insulin sensitivity, serum androgens, LDL and HDL cholesterol, total and truncal body fat mass, and lean mass significantly diverged further from normal over 12 months.

In the 12 metformin-treated girls at risk for PCOS, all these abnormalities significantly reversed within 6 months, and body composition continued to improve between 6 and 12 months as assessed by dual-energy x-ray absorptiometry.